Chemists have a love/hate relationship with protecting and directing groups. See Young, I. S. Baran, P. S. Nature Chemistry, 2009, 1, 193. Although such groups are very often needed to achieve the desired chemo- and regioselectivity of the key chemical transformation in the presence of multiple targets, but like lingering guests, they remain long after they have overstayed their welcome. However, use of such groups is often unavoidable for achieving sufficient selectivity in cascade transformations of multifunctional reactants.
The problem of selectivity comes to the fore in cascades aimed at the preparation of polyaromatic ribbons from conjugated and skipped oligoalkynes. See a) Intermolecular initiation: Alabugin, I. V.; Gilmore, K.; Patil, S.; Manoharan, M.; Kovalenko, S. V.; Clark, R. J.; Ghiviriga, I. J. Am. Chem. Soc. 2008, 130, 11535; b) Intramolecular initiation: Byers, P. M.; Alabugin, I. V. J. Am. Chem. Soc. 2012, 134, 9609; and further see Pati, K.; Hughes, A. M.; Phan, H.; Alabugin, I. V. Chem. Eur. J. 2014, 20, 390. These processes correspond to controlled “polymerization” of alkyne moieties positioned between the two rows of aromatic rings via a selective sequence of “all-exo” cyclizations. See “All endo-dig” cascades require a different activation mode: Byers, P. M.; Rashid, J. I.; Mohamed, R. K.; Alabugin, I. V. Org. Lett. 2012, 14, 6032. Although the regioselectivity of cyclizations is well controlled by the exo-preference for alkyne cyclizations, the key remaining challenge in the design of these cascades involves achieving control over chemoselectivity of initial radical attack. See General discussion of exo-selectivity in radical reactions: a) Beckwith, A. L. J. Tetrahedron 1981, 37, 3073; b) Beckwith, A. L. J.; Schiesser, C. H. Tetrahedron 1985, 41, 3925; General discussion of selectivity of alkyne cyclizations: c) Gilmore, K.; Alabugin, I. V. Chem. Rev. 2011, 111, 6513; d) Alabugin, I. V.; Gilmore, K.; Manoharan, M. J. Am. Chem. Soc. 2011, 133, 12608; e) 5-Exo/6-endo competition in conjugated systems: Alabugin, I. V.; Manoharan, M. J. Am. Chem. Soc. 2005, 127, 12583. The secondary challenge lies in avoiding the formation of pentagonal units at initiation and termination points of the oligoalkyne cascade. We discuss these challenges below.
For the “polymerization cascade” to proceed to completion by utilizing each of the triple bonds, the initial radical attack should proceed exclusively at the central alkyne of the oligoalkyne precursor. See FIG. 1, which is an illustration of the connection between benzannelated oligoalkynes and graphene ribbons. See Beckwith, A. L. J. Tetrahedron 1981, 37, 3073. Such chemoselectivity is difficult to achieve because of the close similarity in the electronic and steric properties of the multiple alkyne units. Initially, we addressed this challenge via covalent attachment of a tethered initiator (“the weak link”) which is directed at the correct alkyne target by geometric restraints imposed by the intramolecular trajectory. See Beckwith, A. L. J.; Schiesser, C. H. Tetrahedron 1985, 41, 3925. Although this approach solves the problem of chemoselectivity of activation, the solution is not ideal because atoms of the tether remain in the molecule after the cascade.
Furthermore, when conjugated oligoalkynes are used as reactants, ring formation from the first two alkyne moieties of benzannelated oligoalkynes, has to proceed via a 5-exo-dig path. See FIG. 2, which illustrates the evolution of molecular design for the conversion of oligoalkynes into polyaromatic ribbons. FIG. 2 includes a depiction of earlier work (“Earlier Work”), and further includes a depiction of the process according to the present invention (“Present Work”). As a consequence, the “polyacetylene ribbon” formed from the oligoalkyne always contained a pentagonal unit.